Nucleic Acids: Biology, Health & Diseases

Biography

Biography: Jonathan Perreault

Abstract

Since the 1990s, hammerhead ribozymes have been studied in regards to gene therapy because of their simple RNA-cleaving catalytic property and the relative ease with which they could be designed to target mRNAs through sequence modifications permitting base complementarity with the RNA to be cleaved. Since then, the discovery of RNA interference and CRISPR have relegated ribozymes behind, while spurring a renewed interest in noncoding RNA-mediated gene therapy. However, meanwhile advances in design and major discoveries on hammerhead ribozymes, such as better activity when stem I and II interact, have opened new avenues. We have demonstrated the high efficiency of hammerhead ribozymez by using combinations that target the same mRNA. Moreover, the automated design software, RiboSoft, streamlines the use of ribozymes for gene knockdowns. Results of RNA targeting against PABPN1, a gene involved in hereditary diseases, and other RNAs will be shown. Ribozymes have many advantages over RNAi and CRISPR: they are inherently active and do not rely on any accessory protein or component, making them easily portable to any organism; since they do not require processing and rely on structure for their activity, other modules can be added for their function; and they can be assayed in vitro. In short, the revived interest in using RNA for gene therapy is likely to also help ribozymes make a come back by stimulating research for general problems such as gene delivery.